Interest within the industry in providing various vehicles for the slow delivery of active ingredients to the body has resulted in a variety of bioadhesive delivery forms. Various types of materials found to adhere to mucous membranes without exerting a harmful effect have been formed into tablets designed to provide a delivery system for the administration of drugs over a period of time. Ideally the drug, or other active agent, is incorporated into a bioadhesive tablet and the tablet is placed in contact with a mucous membrane to which it adheres. The drug, or other active agent, is dissolved from the tablet and delivered into a body cavity or into the body through the mucous membrane. A problem associated with such a delivery system is related to the tenacity with which the tablet adheres to the mucous membrane. Sometimes the tablet becomes separated from the mucous membrane before the desired dose of active material has been completely delivered.
U.S. Pat. No. 3,996,934 issued to Zaffaroni on December 14, 1976 discloses a bandage for continuously administering controlled quantities of systemically active drugs through the skin or mucosa. The bandage comprises a laminate of (1) a backing member defining one surface of the bandage, and, defining the other face surface of the bandage, (2) at least one reservoir comprised of a systemically active drug formulation confined within a wall member, and (3) means to secure the bandage. The wall member is formed from drug release rate controlling material to continuously meter the flow of a therapeutically effective amount of drug from the reservoir to the skin or mucosa at a controlled and predetermined rate over a prolonged period of time.
U.S. Pat. No. 4,226,848 and U.S. Pat. No. 4,250,163 issued to Nagai et al on Oct. 7, 1980, and Feb. 10, 1981, respectively, are directed to a method for administering a medicament which comprises adhering to the mucosa of the oral or nasal cavity a pharmaceutical preparation comprising (a) a water-swellable and mucosa-adhesive polymeric matrix, and (b) a pharmaceutically effective amount of the medicament dispersed therein. The polymeric matrix comprises about 50-95% by weight of a cellulose ether and about 50 to 5% by weight of a homo or copolymer of acrylic acid or a pharmaceutically acceptable salt thereof. According to this patent, the pharmaceutical preparation may further contain at least one known excipient such as a lubricant, binder, vehicle, coloring agent, taste controlling agent and color controlling agent as required for improving the appearance, odor or taste of the pharmaceutical preparation. The lubricants include talc, stearic acid, stearate salts, and waxes. Examples of the binders include starch, dextrin, tragacanth, gelatin, polyvinyl pyrrolidone and polyvinyl alcohol. The vehicles include starch, crystalline cellulose, dextrin, mannitol, sorbitol, and anhydrous calcium phosphates. The agents for controlling tastes and smells are citric acid, fumaric acid, tartaric acid, menthol, and citrus perfumes.
U.S. Pat. No. 4,286,592 issued to Chandrasekaran on Sept. 1, 1981 is directed to a bandage for administering drugs to the skin. The bandage is a laminate of a backing layer, a drug reservoir layer, and a contact adhesive layer. The bandage consists essentially of a sandwich type laminate of: (a) a backing lamina that is substantially impermeable to the drug, one face of which forms the top of the bandage; (b) a drug reservoir lamina adjacent the opposite face of the backing layer comprising the drug dispersed in a carrier that is permeable to the drug; and (c) a contact adhesive lamina adjacent and below the drug reservoir lamina comprising a contact adhesive composition that is permeable to the drug.
U.S. Pat. No. 4,292,299 issued to Suzuki et al on Sept. 29, 1981 is directed to a slow-releasing medical preparation to be administered by adhering to the wet mucous surface comprising an adhesive layer and a nonadhesive layer. The adhesive layer is composed of a polymer which has the adhesiveness to the wet mucous surface and a property to swell upon moistening. The nonadhesive layer is either water soluble or disintegrable which has no adhesiveness to the wet mucous surface. At least one of the layers has a medicament. Polymers disclosed as useful for the adhesive layer include homopolymers of acrylic acid; copolymers of acrylic acid; hydrophilic vinyl polymers; hydrophilic cellulose derivatives; polysaccharides such as hydroxypropyl starch, alginic acid, sodium alginate, and tragacanth gum or their derivatives; and such derivatives having improved swellability as collagen, gelatine or radiobridged gelatine, and chemically modified gelatine. The adhesive layer may further contain other ingredients such as a binder, disintegrator, coloring agent, corrigent, and lubricant provided that the layer maintains said adhesiveness to the wet mucous surface. Examples of ingredients which may comprise the nonadhesive layer include lactose, glucose, sucrose, starch, crystalline cellulose, dextrin, cyclodextrin, silicic acid anhydride, aluminum silicate, talc, calcium stearate, magnesium stearate, beeswax, polyethylene glycol, and polyphosphate. The lubricants which may be mentioned and which are used as occasion demands are talc, stearic acid, stearate salts, and waxes. The binders include, for instance, starch, dextrin, tragacanth, gelatine, polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose, crystalline cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, carboxymethyl cellulose, etc. The disintegrators include starch, crystalline cellulose, calcium carboxymethyl cellulose, etc. The excipients include starch, crystalline cellulose, dextrin, lactose, mannitol, sorbitol, calcium phosphoric acid anhydride, etc. The corrigents include citric acid, fumaric acid, tartaric acid, menthol, citrus perfumes, etc.
U.S. Pat. No. 4,572,832 issued to Kigasawa et al on Feb. 25, 1986 is directed to a soft buccal containing a pharmaceutically effective amount of a medicament to be absorbed through the oral mucosa, a water-soluble protein, a polyhydric alcohol, and a fatty acid ester and/or a carboxyvinyl polymer. The water-soluble protein includes natural proteins of animal or plant origin and non-natural ones which are artificially produced peptides. The polyhydric alcohol includes glycols, triols and polyols. The polyhydric alcohols include cellulose and sugars. Typical of the sugars are monosaccharides, disaccharides and polysaccharides. The monosaccharides include glucose, galactose, fructose, mannose, mannitol, and sorbitol. The disaccharides may be the dimers of such monosaccharides as maltose, lactose and sucrose. The polysaccharides include the genuine polysaccharides which are condensates of at least 7 units of the above-mentioned monosaccharides such as starch and its derivatives, dextrin, dextran, chitin, alginic acid, glycogen, etc., and the composite condensates of at least 7 units of one of the abovementioned monosaccharides with one of non-sugar substances such as mannan, pectin, gum arabic, etc. Other additives which may be used include, flavors (saccharin sodium, glycyrrhizin, malt syrup, citric acid, tartaric acid, menthol, lemon oil, citrus flavor, common salt, etc.); stabilizers/preservatives; colors; excipients/disintegration adjusting agents; water-soluble polymers other than water-soluble proteins; and stearic acid and its salts, talc, palmitic acid, and other substances known as emulsifiers, dispersants, binders, thickeners, etc.
U.S. Pat. No. 4,597,959 issued to Barr on July 1, 1986 discloses a breath freshener composition, in a wafer form having slow release. The composition comprises a multiplicity of microencapsulated liquid droplets of flavoring materials. The microencapsulated droplets are soluble in saliva to slowly release the flavoring materials. The microencapsulates are present in a wafer form which comprises a base of gelatin, gum arabic and/or Carrageenen with an adhesive distributed throughout. In this way the wafer can be directly applied to the gums and palate or the wafer can be directly applied to the inner or outer surfaces of full or partial dentures.
U.S. Pat. No. 4,615,697 issued to Robinson on Oct. 7, 1986 discloses controlled release compositions and methods utilizing those compositions. The compositions include a bioadhesive and an effective amount of a treating agent. The bioadhesive comprises a water-swellable, but water-insoluble, fibrous, cross-linked carboxy-functional polymer. In typical practice, the ratio by weight of the bioadhesive to the treating agent in the composition is about 200,000:1 to about 1:100.
British Patent Specification No. 1,240,411 whose complete specification was published July 21, 1971 discloses a tab for application to the mucous membrane which tab is capable of adhering thereto by moisture. The tab is saturated with or coated with at least one anaesthetic agent, disinfectant agent and dye for marking the membrane. Generally, the tab is formed from paper, textile material, plastics material or a mixture thereof. Coating may be with the aid of an adhesive such as albumin, tragacanth or a cellulose adhesive.
U.K. Patent Application No. GB 2156215A published on Oct. 9, 1985 discloses a percutaneous absorption type preparation which comprises a backing and an adhesive layer. The backing is readily conformable to skin or mucosa and is substantially impermeable to a drug absorbed through the skin or mucosa. The adhesive layer comprises a polymer which is pressure-adhesive at room temperature, and a drug present in the polymer. The drug is present in the adhesive layer in an amount greater than its saturated solubility in the polymer and the excess amount of the drug greater than the saturated solubility is dispersed in the polymer in the form of re-crystallized fine particles having a substantially uniform size.
U.K. Patent Application No. GB 2161073A published Jan. 8, 1986 discloses a transdermal therapeutic system adapted for the delivery of biologically active agents for an extended time period comprising, in combination, a matrix containing the agent uniformly distributed therein with the intended body distal surface of said matrix having a fibrous reinforcing means imbedded therein. The matrix being capable of adherence to the skin with a peel strength sufficient to maintain the system in place for the extended time and being sufficiently low to be removed without discomfort.
Thus, buccal tablets possessing the ability to adhere to the oral mucosa and release active agents (drug or cosmetic) to the oral cavity are known in the art. The tablets are composed of a variety of natural or synthetic polymeric materials. In formulating the compositions for such tablets attention is focused on providing tablets which are adherent during the period of use, i.e., stay in place, are capable of continued release of an active ingredient over a desired time period, and are comfortable to the user. Thus, a novel composition which provides improved adhesion and is capable of continual release of an active ingredient would be a welcome contribution to the art. This invention provides such a composition.